© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
Vascular endothelial growth factor-D expression in human atherosclerotic lesions
aDepartment of Molecular Medicine, A.I. Virtanen Institute, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland
bDepartment of Cardiovascular Surgery, University of Kuopio, Kuopio, Finland
cProvincial State Office of Eastern Finland, Kuopio, Finland
dLudwig Institute for Cancer Research, Post Office Royal Melbourne Hospital, Parkville, Victoria 3050, Australia
eMolecular/Cancer Biology Laboratory, Biomedicum, University of Helsinki, Helsinki, Finland
fDepartment of Medicine, University of Kuopio, Kuopio, Finland
gGene Therapy Unit, Kuopio University Hospital, Kuopio, Finland
seppo.ylaherttuala{at}uku.fi
* Corresponding author. Tel.: +358-17-162-075; fax: +358-17-163-751.
Objective: Vascular endothelial growth factor-D (VEGF-D) is a recently characterized member of the VEGF family, but its expression in atherosclerotic lesions remains unknown. We studied the expression of VEGF-D and its receptors (VEGFR-2 and VEGFR-3) in normal and atherosclerotic human arteries, and compared that to the expression pattern of VEGF-A. Methods: Human arterial samples (n=39) obtained from amputation operations and fast autopsies were classified according to the stage of atherosclerosis and studied by immunohistochemistry. The results were confirmed by in situ hybridization and RT-PCR. Results: We found that while VEGF-A expression increased during atherogenesis, VEGF-D expression remained relatively stable only decreasing in complicated lesions. In normal arteries and in early lesions VEGF-D was mainly expressed in smooth muscle cells, whereas in complicated atherosclerotic lesions the expression was most prominent in macrophages and also colocalized with plaque neovascularization. By comparing the staining profiles of different antibodies, we found that proteolytic processing of VEGF-D was efficient in the vessel wall. VEGFR-2, but not VEGFR-3, was expressed in the vessel wall at every stage of atherosclerosis. Conclusions: Our results suggest that in large arteries VEGF-D is mainly expressed in smooth muscle cells and that it may have a role in the maintenance of vascular homeostasis. However, in complicated lesions it was also expressed in macrophages and may contribute to plaque neovascularization. The constitutive expression of VEGFR-2 in arteries suggests that it may be one of the principal mediators of the VEGF-D effects in large arteries.
KEYWORDS Arteries; Atherosclerosis; Gene expression; Growth
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